The adoptive transfer of tumor infiltrating lymphocytes (TIL) can mediate tumor regression in patients with metastatic melanoma, suggesting that tumor rejection antigens recognized by T cells exist on these tumor cells. The availability of such T cells has made it possible to clone and sequence the genes that encode human melanoma antigens. The antigens identified so far from human melanoma can be divided into two classes based on their expression pattern. The antigens of the first class are encoded by genes that are expressed only in tumor and testis, but not other normal human tissues. MAGE1, MAGE3, GAGE and BAGE are examples of this class. The second class of antigens represents differentiation antigens encoded by genes that are expressed only in melanocytes, melanomas, and normal retina. MART-1/Melan-A, gp100 and tyrosine are examples of this class. All these antigens are nonmutated self proteins. However, several mutated antigens were also identified to be recognized by T cells, including CDK 4, B-catenin and Mum-1. Identification of the antigenic epitopes recognized by T cells derived from the corresponding gene products is important not only for understanding the mechanism of immune response to self antigens, but also for developing new, effective immunotherapeutic strategies with these antigens or synthetic peptides for the treatment of patients with cancer.
Previous studies showed that the infusion of TIL586 plus IL-2 into the autologous patient with melanoma resulted in the objective regression of metastases. More recently, the gene, tyrosinase-related protein 1 (TRP-1 or gp75) was cloned which encodes the tumor antigen recognized by TIL586 in association with HLA-A31. Interestingly, the gene product, gp75, was originally identified as an antigen recognized by IgG antibodies in the serum from a patient with metastatic melanoma. The gene was found to be expressed only in melanoma, normal melanocyte cell lines, and retina, but not in other normal tissues tested. Therefore, this gene is a member of the second class of antigens including MART-1/Melan-A, gp100 and tyrosinase.
Wang, R. F. et al J. Exp. Med. Vol. 183, pp. 1131–1140 (1996) report on the identification of a cancer peptide encoded from an alternative open reading frame sequence within the TRP-1 gene which is specifically recognized by cloned TIL 586 cells. Wang, R. F. et al J. Exp. Med. Vol 184, pp. 2207–2216 (1996) identified a second tumor antigen, TRP-2, recognized by a HLA-A31-restricted CTL clone derived from the TIL 586 cell line.
The present invention is the identification and isolation of novel tumor antigens distinct from TRP-1 and TRP-2 which are recognized by CTL clones derived from the TIL 586 cell line. The cancer peptides of the invention are useful as an immunogen and vaccine to inhibit or prevent cancer in a mammal and as a diagnostic agent to detect cancer or precancer.